WCLC 2025 - Posters & ePosters-P3.18.70 Combination of Osimertinib and Carotuximab for Advanced, EFGR-Mutated Non-Small Cell Lung Cancer Patients

Pdf Summary

This trial-in-progress (NCT05401110) at Cedars-Sinai Medical Center investigates the safety and efficacy of combining osimertinib, an EGFR tyrosine kinase inhibitor (TKI), with carotuximab, an anti-CD105 monoclonal antibody, in advanced EGFR-mutated non-small cell lung cancer (NSCLC). High expression of CD105 (endoglin), a protein upregulated in proliferating endothelial cells and involved in bone morphogenic protein signaling, correlates with poorer overall survival in EGFR-mutant NSCLC patients. Notably, EGFR-TKI treatment itself increases CD105 levels, which can contribute to resistance.<br /><br />Preclinical models demonstrated that inhibiting CD105 with carotuximab restores sensitivity to osimertinib and suggests synergistic effects of the combination to potentially overcome acquired TKI resistance. The trial aims to enroll 60 patients with stage IV or recurrent non-squamous NSCLC harboring EGFR activating mutations, including those with progression on prior EGFR TKIs or persistent circulating tumor DNA (ctDNA) after frontline osimertinib.<br /><br />The primary objective is to assess safety and identify the recommended Phase 2 dose (RP2D) of the drug combination. Secondary goals include evaluating response rates, duration of response, progression-free survival, and disease control rates. Exploratory analyses will examine whether CD105-positive extracellular vesicles and plasma soluble CD105 levels predict treatment benefit.<br /><br />The study employs a dose-escalation design for carotuximab with fixed or reduced osimertinib doses, followed by expansion cohorts focusing on patients with prior progression or persistent ctDNA. Preliminary enrollment reached seven patients as of August 2025. Ongoing work aims to validate this novel therapeutic strategy targeting the CD105 axis to improve outcomes in EGFR-mutated NSCLC resistant to current TKIs.<br /><br />Funding is provided by the William and Anna Tenenblatt Foundation and Cedars-Sinai Cancer Center. Key reference includes a 2025 Drug Resistance Updates publication detailing preclinical findings supporting this combination approach.

Asset Subtitle

Karen Reckamp

Meta Tag

Speaker Karen Reckamp

Topic Clinical Trials in Progress

Keywords

osimertinib

carotuximab

EGFR-mutated non-small cell lung cancer

CD105

EGFR tyrosine kinase inhibitor

TKI resistance

clinical trial NCT05401110

phase 2 dose

circulating tumor DNA

dose-escalation study